role of genetic susceptibility in the etiology of lung cancer in two distinct studies. The first is a case-control study of African-Americans and Caucasians in Los Angeles County. Subject enrollment (356 cases and 731 control subjects) was completed by S. London while she was a faculty member at University of Southern California. In the past year we published results on microsomal epoxide hydrolase. We are currently conducting laboratory analyses of polymorphisms in the DNA repair genes XPD, XRCC1 and XRCC3. The other study is a cohort study of Chinese men in Shanghai. This project is collaborative with investigators at USC and Shanghai. Using prospectively collected samples, we examined the relation between isothiocyanates and lung cancer risk and observed a gene-diet interaction. Isthiocyanates have been shown to inhibit tobacco related lung carcinogenesis in laboratory animals, but human data are sparse. Chinese populations are high consumers of brassica vegetables, the sources of isothiocyantes, compared with Western populations. Using a new urinary biomarker of intake, we found that higher levels of isothiocyanates protected against lung cancer, but primarily among subjects genetically deficient in glutathione transferase M1 (GSTM1), which rapidly eliminates these beneficial compounds. We have also examined associations between a polymorphism of CYP1A1 and lung cancer risk in this Shanghai cohort. The prevalence of this polymorphism is relatively high in Chinese populations. A number of publications have emerged from the study of genetic polymorphisms and lung cancer risk in African-Americans and Caucasians - 14 to date. In the past year, we have published results on microsomal epoxide hydrolase. In the Shanghai cohort study, we have identified a novel gene-diet interaction between a biologic marker of isothiocyanate intake and genetic polymorphisms of GSTM1. This is the first study to use a biomarker of isothiocyanate intake in relation to the risk of cancer and provides important evidence in humans for lung cancer chemoprevention by isothiocyanates which had previously been documented in animals. It is among the first data to show gene-diet interaction in lung cancer. We have also found that a variant allele of CYP1A1 which occurs at higher frequency in Chinese than Caucasians, may play a role in lung cancer risk, particularly among lighter smokers subjects who are also deficient in GSTM1. This work is in press.